- Volume 16 Issue 9
DOI QR Code
Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study
- Uncu, Dogan (Department of Medical Oncology, Education and Research Hospitals) ;
- Bayoglu, Ibrahim Vedat (Department of Medical Oncology, Education and Research Hospitals) ;
- Arslan, Ulku Yalcintas (Department of Medical Oncology, Education and Research Hospitals) ;
- Kucukoner, Mehmet (Dicle University Faculty of Medicine) ;
- Artac, Mehmet (Necmettin Erbakan University Faculty of Medicine) ;
- Koca, Dogan (Department of Medical Oncology, Education and Research Hospitals) ;
- Oguz, Arzu (Department of Medical Oncology, Education and Research Hospitals) ;
- Demirci, Umut (Department of Medical Oncology, Education and Research Hospitals) ;
- Arpaci, Erkan (Department of Medical Oncology, Education and Research Hospitals) ;
- Dogan, Mutlu (Department of Medical Oncology, Education and Research Hospitals) ;
- Kucukzeybek, Yuksel (Department of Medical Oncology, Education and Research Hospitals) ;
- Turker, Ibrahim (Department of Medical Oncology, Education and Research Hospitals) ;
- Isikdogan, Abdurrahman (Dicle University Faculty of Medicine) ;
- Guler, Tunc (Necmettin Erbakan University Faculty of Medicine) ;
- Zengin, Nurullah (Department of Medical Oncology, Education and Research Hospitals)
- Published : 2015.05.18
Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.
Breast cancer;metastatic;HER2 positive;trastuzumab;lapatinib;retreatment
- Bartsch R, Rottenfusser A, Wenzel C, et al (2007). Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J Neurooncol, 85, 311-7. https://doi.org/10.1007/s11060-007-9420-5
- Blackwell KL, Burstein HJ, Storniolo AM, et al (2010). Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol, 28, 1124-0. https://doi.org/10.1200/JCO.2008.21.4437
- Burris HA, Rugo HS, Vukelja SJ, et al (2011). Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol, 29, 398-405. https://doi.org/10.1200/JCO.2010.29.5865
- Cabuk D, Basaran G, Teomete M, et al (2014). Clinical outcome of Turkish metastatic breast cancer patients with currently available treatment modalities-single center experience. Asian Pac J Cancer Prev, 15, 117-22. https://doi.org/10.7314/APJCP.2014.15.1.117
- Cancello G, Montagna E, D'Agostino D, et al (2008). Continuing trastuzumab beyond disease progression: outcomes analysis in patients with metastatic breast cancer. Breast Cancer Res, 10, 60.
- Chariyalertsak S, Purisa W, Vinyuvat S (2011). Her-2/neu amplification determined by real-time quantitative PCR and its association with clinical outcome of breast cancer in Thailand. Asian Pac J Cancer Prev, 12, 1703-6.
- Crown J, Casey M A, Cameron D, et al (2009). Lapatinib (L) plus capecitabine (C) in HER2+ metastatic breast cancer (MBC): exploratory analyses by prior therapy. Eur J Cancer, 7, 5082.
- Extra JM, Antoine EC, Vincent-Salomon A, et al (2010). Efficacy of trastuzumab in routine clinical practice and after progression for metastatic breast cancer patients: the observational Hermine study. Oncologist, 15, 799-809. https://doi.org/10.1634/theoncologist.2009-0029
- Geyer CE, Forster J, Lindquist D, et al (2006). Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med, 355, 2733-43. https://doi.org/10.1056/NEJMoa064320
- Ghaffari SR, Sabokbar T, Dastan J, et al (2011). Her2 amplification status in Iranian breast cancer patients: comparison of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). Asian Pac J Cancer Prev, 12, 1031-4.
- Gori S, Montemurro F, Spazzapan S, et al (2012). Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer. Ann Oncol, 23, 1436-41. https://doi.org/10.1093/annonc/mdr474
- Kirsch DG, Ledezma CJ, Mathews CS, et al (2005). Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol, 23, 2114-6; author reply 6-7. https://doi.org/10.1200/JCO.2005.05.249
- Marty M, Cognetti F, Maraninchi D, et al (2005). Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol, 23, 4265-74. https://doi.org/10.1200/JCO.2005.04.173
- Pestalozzi BC, Zahrieh D, Price KN, et al (2006). Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol, 17, 935-44. https://doi.org/10.1093/annonc/mdl064
- Revillion F, Bonneterre J, Peyrat JP (1998). ERBB2 oncogene in human breast cancer and its clinical significance. Eur J Cancer, 34, 791-808. https://doi.org/10.1016/S0959-8049(97)10157-5
- Sawrie SM, Meredith RF, Spencer RA, et al (2007). "HER2-neu status as a predictor of survival in patients with brain metastases from primary breast adenocarcinoma." Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 25, No 18S (June 20 Supplement): 1016.
- Scaltriti M, Verma C, Guzman M, et al (2009). Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene, 28, 803-14. https://doi.org/10.1038/onc.2008.432
- Sendur MAN, Aksoy S, Ozdemir NY, et al (2012). What is the mechanism of progression with trastuzumab treatment--escape or resistance? Asian Pac J Cancer Prev, 13, 5915-6. https://doi.org/10.7314/APJCP.2012.13.11.5915
- Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
- Singhai R, Patil V, Patil A (2011). Immunohistochemical (IHC) HER-2/neu and fluorescent-in situ hybridization (FISH) gene amplification of breast cancer in Indian women. Asian Pac J Cancer Prev, 12, 179-83.
- Slamon DJ, Leyland-Jones B, Shak S, et al (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 344, 783-92. https://doi.org/10.1056/NEJM200103153441101
- Spazzapan S, Crivellari D, Tumolo S, et al (2010). Retreatment with trastuzumab after progression on lapatinib-based therapy in heavily pretreated HER2-positive metastatic breast cancer: a monoinstitutional experience. J Clin Oncol, 28, 15S Abstr 1082.
- Stemmler HJ, Kahlert S, Siekiera W, et al (2005). Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC). Onkologie, 28, 582-6. https://doi.org/10.1159/000088296
- Swain SM, Kim SB, Cortes J, et al (2013). Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol, 14, 461-71. https://doi.org/10.1016/S1470-2045(13)70130-X
- Therasse P, Arbuck SG, Eisenhauer EA, et al (2000). New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Natl Cancer Inst, 92, 205-16. https://doi.org/10.1093/jnci/92.3.205
- Trotti A, Byhardt R, Stetz J, et al (2000). Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys, 47, 13-47. https://doi.org/10.1016/S0360-3016(99)00559-3
- Verma S, Miles D, Gianni L, et al (2012). Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med, 367, 1783-91. https://doi.org/10.1056/NEJMoa1209124
- von Minckwitz G, du Bois A, Schmidt M, et al (2009). Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol, 27, 1999-2006. https://doi.org/10.1200/JCO.2008.19.6618
- Zhuo WL, Zhang L, Xie QC, et al (2014). Identifying differentially expressed genes and screening small molecule drugs for lapatinib-resistance of breast cancer by a bioinformatics strategy. Asian Pac J Cancer Prev, 15, 10847-53.